The incidence of diseases of affluence, such as diabetes mellitus, cardiovascular diseases, high blood pressure, and high cholesterol has been reported to rise. Consequently, the concentrations of residues of drugs designed to treat these diseases have been rising in water bodies. Moreover, the toxicity of these pharmaceuticals towards fish and other non-target organisms can be even enhanced by microplastic particles that are reportedly present in surface water. Therefore, the aim of this study was to describe the effects of three highly prescribed drugs, in particular metoprolol, enalapril, and metformin on fish early-life stages. Also, it was hypothesized that polystyrene microparticles will increase the toxicity of metoprolol to fish early-life stages. Embryonal acute toxicity tests on Danio rerio and Cyprinus carpio were carried out in order to describe the possible toxic effects of metoprolol, enalapril, and metformin. Also, the acute toxicity of polystyrene microparticles and the combination of metoprolol with polystyrene microparticles were tested on D. rerio embryos. Additionally, a 31-day long embryo-larval subchronic toxicity test was carried out with C. carpio in order to describe the long-term effects of low concentrations of metoprolol. The results of the study show that both metoprolol and enalapril have the potential to disrupt the early development of the heart in the embryonal stages of fish. Also, enalapril and metformin together with polystyrene microparticles seem to possibly disrupt the reproduction cycle and act as endocrine disruptors. Both pure polystyrene microparticles and the combination of them with metoprolol affect inflammatory processes in organisms. Additionally, metformin alters several metabolism pathways in fish early-life stages. The results of the study bring new evidence that even low, environmentally-relevant concentrations of pharmaceuticals have the potential to disrupt the early development of fish, particularly on a molecular level.

Department of Anatomy Histology and Embryology Faculty of Veterinary Medicine University of Veterinary Sciences Brno Czech Republic

Department of Animal Protection and Welfare and Veterinary Public Health Faculty of Veterinary Hygiene and Ecology University of Veterinary Sciences Brno Czech Republic

Department of Animal Protection and Welfare and Veterinary Public Health Faculty of Veterinary Hygiene and Ecology University of Veterinary Sciences Brno Czech Republic; Department of Infectious Diseases and Preventive Medicine Veterinary Research Institute Brno Czech Republic

Department of Animal Protection and Welfare and Veterinary Public Health Faculty of Veterinary Hygiene and Ecology University of Veterinary Sciences Brno Czech Republic; Department of Zoology Fisheries Hydrobiology and Apiculture Faculty of Agrisciences Mendel University in Brno Brno Czech Republic; Department of Animal Breeding Animal Nutrition and Biochemistry Faculty of Veterinary Hygiene and Ecology University of Veterinary Sciences Brno Czech Republic

Department of Aquaculture Faculty of Fisheries Kastamonu University Kastamonu Turkiye

Department of Infectious Diseases and Preventive Medicine Veterinary Research Institute Brno Czech Republic

Department of Pharmacology and Toxicology Veterinary Research Institute Brno Czech Republic

Department of Zoology Fisheries Hydrobiology and Apiculture Faculty of Agrisciences Mendel University in Brno Brno Czech Republic

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